Synergistic actions of pentobarbital and dihydropyridine Ca2+ antagonists on guinea pig isolated thoracic aorta.
Fundam Clin Pharmacol
; 11(5): 448-53, 1997.
Article
em En
| MEDLINE
| ID: mdl-9342598
ABSTRACT
In order to elucidate the mechanism(s) behind the interactions between barbiturates and Ca2+ antagonists, the effects of pentobarbital combined with three structurally diverse types of Ca2+ antagonist on CaCl2-induced contractile responses of the guinea pig thoracic aorta in Ca(2+)-free and 40 mM K+ medium and the effects of pentobarbital on Ca2+ antagonist binding to guinea pig aortic membranes were investigated. The dihydropyridine derivatives isradipine (10(-10)-10(-8) M) and nifedipine (10(-10)-10(-8) M) inhibited CaCl2-induced contractions concentration-dependently. Treatment with both pentobarbital (10(-4) M) and dihydropyridine Ca2+ antagonists (10(-9) M) shifted the CaCl2 concentration-response curves to the right significantly compared with those after treatment with the Ca2+ antagonists and pentobarbital alone. However, no synergistic effects of pentobarbital (10(-4) M) with other types of Ca2+ antagonist (verapamil (10(-7) M) and diltiazem (10(-6) M)) were observed. The binding of [3H]isradipine (2 x 10(-9) M) to guinea pig aortic membranes was increased significantly by simultaneous pentobarbital treatment, but no such effect was observed with [3H]verapamil (10(-8) M) or [3H]diltiazem (2 x 10(-8) M). These findings suggest that the synergistic contractile effects of pentobarbital and dihydropyridines were, in part, due to enhancement of dihydropyridine binding to guinea pig aortic membranes (L-type Ca2+ channels) by pentobarbital and that the interactions between pentobarbital and Ca2+ antagonists may be structurally specific.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pentobarbital
/
Bloqueadores dos Canais de Cálcio
/
Nifedipino
/
Isradipino
/
Músculo Liso Vascular
Limite:
Animals
Idioma:
En
Revista:
Fundam Clin Pharmacol
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Japão